Metabolic engineering of plant medicines

For centuries, plants have provided a broad palette of molecules essential to human medicine for the treatment of various illnesses such as infectious diseases, neurodegenerative disorders

and cancers. However, manufacturing these precious medicines has always been challenging. Indeed, plant-derived pharmaceutical drugs often display complex structures, precluding their

chemical synthesis at industrial scales. In addition, these compounds accumulate naturally in minute amounts in the source plants, which explains their unsustainable and highly costly

supply. The emergence of synthetic biology in the early 2000s opened up alternative routes to produce prominent plant-derived medicines. In 2006, Ro et al. published a seminal article in

Nature reporting the biosynthesis of a complex plant natural product to treat malaria by an engineered microorganism.

Malaria kills hundreds of thousands of people each year. Treatment with the highly valuable molecule artemisinin and its derivatives has dramatically reduced this death toll, as acknowledged

with the 2015 Nobel Prize in Physiology or Medicine awarded to Tu Youyou. However, the effect of such a treatment has been hampered by restricted access to the source plant, the annual

wormwood Artemisia annua. Ro et al., with the Keasling laboratory, developed a game-changing approach by creating a yeast strain capable of synthesizing artemisinic acid, a precursor of the

antimalarial drug.

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